The Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS). HIV entry into cells involves formation of a complex between the HIV envelope glycoprotein (Env, which consists of a complex containing the HIV glycoproteins gp120 and gp41; gp120-gp41), a cell-surface receptor (CD4), and a cell-surface co-receptor (e.g., the chemokine receptor CCR5 or CXCR4). Binding of Env to CD4 and either co-receptor initiates a series of conformational changes that are the heart of the fusion machinery leading to viral entry into the target cell. Therefore, efforts to develop a vaccine for the prevention and/or treatment of HIV infection have focused upon the development of neutralizing antibodies that specifically bind to Env. However, the extensive variation of Env in the numerous isolates of HIV so far identified presents a major obstacle in designing an effective immunogen for the isolation of antibodies with broadly neutralizing activity against multiple HIV isolates.
Currently there are only three well-characterized monoclonal antibodies (mAbs) with broadly neutralizing activity: the anti-gp120 mAbs b12 (Burton et al. Science 266:1024–1027, 1994) and 2G12 (Trkola et al. J. Virol. 70:1100–1108, 1996), and the anti-gp41 mAb 2F5 (Conley et al. Proc. Natl. Acad. Sci. U.S.A. 91:3348–3352, 1994). Given the ever-increasing number of people infected with HIV, there is a need in the art for additional antibodies with broadly neutralizing activity against HIV, which can be used as passive immunotherapy or passive immunoprophylaxis to treat, ameliorate, inhibit, or prevent HIV infections in individuals who have, or who at risk for developing, such infections. Furthermore, there is a need in the art for new strategies by which to identify and/or isolate such broadly neutralizing anti-HIV antibodies.